Download Email Submission: Robert Oppenheimer 1. Which option/s do you

Email Submission: Robert Oppenheimer
1. Which option/s do you support, and why?
Option 4.
In the long term, I think it should become the goal of the OGTR to focus on biological
properties. By analogy, we do not assess the safety of chemicals by the process used
to synthesise them, but instead by whether a chemical has properties that render it
hazardous to human health and whether there are appropriate measures to decrease the
risk of accidents. Future biotechnologies will only become more complex and diverse
as genetic technologies are invented or repurposed from Nature. As such, it is
wasteful and ineffective to focus on process when time and energy should be devoted
to considering the biological properties considered safe.
In the short term, gene-editing is a quicker, safer version of natural or chemical
mutations and should be regulated accordingly, ie, it should be generally permissible
in non-human organisms. Where sufficient information is known about genotypephenotype relationships, it will be more cost-effective than traditional breeding
methods to achieve the same result (Carlson et al. 2016). Tracking the use, users,
purpose and consequences of gene-editing would be desirable where it is feasible and
legal.
Option 4 seems to me to resonate most with this reasoning, as it focuses on the
outcomes of genetic modification - the properties of the modified organisms.
Carlson, D. F., Lancto, C. A., Zang, B., Kim, E. S., Walton, M., Oldeschulte, D., ... &
Fahrenkrug, S. C. (2016). Production of hornless dairy cattle from genome-edited cell
lines. Nature biotechnology, 34(5), 479-481.
4. How might options 2-4 change the regulatory burden on you from the gene
technology regulatory scheme?
I imagine that researchers may find it very frustrating if an arbitrary regulation is
imposed - i.e., if a routine single nucleotide edit that is known to have occurred by
naturally by other mechanisms requires a detailed and time-consuming safety
inspection. I imagine that some researchers would consider working with
collaborators in countries with less stringent regulations, setting up wasteful or
elaborate schemes to post edited DNA or organisms internationally, or moving
overseas.
6. Might contained laboratory research on GM gene drive organisms pose
different risks to other contained research with GMOs, and how could these
risks be managed? Supporting information and science-based arguments should
be provided where possible.
Gene drives have existing analogues in Nature (eg, the super-Mendelian inheritance
of homing endonucleases), which were discovered before they inspired synthetic
biologists. It is reasonable to expect synthetic gene drives will have similar
evolutionary pressures as natural gene drives (Burt, 2003). Once they reach fixation in
a population, there will be little to no evolutionary pressure to maintain the specific
sequence which led to fixation (Goddard & Burt, 1999). This will lead to
degeneration of the gene drive and any associated genes by random mutation, leading
to complete silencing and less frequently to the reemergence of new gene drives with
a different genetic sequence.
We should expect synthetic gene drives will continue to evolve long after they have
propagated a ‘useful’ genetic cargo through a population. This implies that if a
contained laboratory experiment is carried out over a long enough time, unintentional
release should occur eventually with a finite probability. Similarly, intentionally
released gene drives will inevitably evolve and be horizontally transferred to related
species. If the time-scale for such events (<106 years) greatly exceeds the time-scale
in which a gene-drive may be useful (say, 10-100 years), and if the transfer of a gene
drive to a related species will not result in any undesirable effects, then
there should be little safety concern.
However, if it is desirable to limit the entry of synthetic gene drives into the human
gene pool, then strict regulations should be made to avoid the creation of gene drives
targeting primates or domesticated species that have frequent contact with people.
Goddard, M. R., & Burt, A. (1999). Recurrent invasion and extinction of a selfish
gene. Proceedings of the National Academy of Sciences, 96(24), 13880-13885.
Burt, A. (2003). Site-specific selfish genes as tools for the control and genetic
engineering of natural populations. Proceedings of the Royal Society of London B:
Biological Sciences, 270(1518), 921-928.
8. Do you have proposals for amendments to any other technical or scientific
aspects of the GT Regulations? All proposals should be supported by a rationale
and a science-based argument.
In the long term, it should become the goal of the OGTR to focus on biological
properties. By analogy, we do not assess the safety of chemicals by the process used
to synthesise them, but instead by whether a chemical has properties that render it
hazardous to human health and whether there are appropriate measures to decrease the
risk of accidents. Future biotechnologies will only become more complex and
entangled as diverse genetic technologies are invented or repurposed from natural
processes of genetic change. As such, it is wasteful and ineffective to focus on process
when time and energy should be devoted to considering the biological properties
considered safe.